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N. Di Girolamo, M. Sarris, M. T. Coroneo, D. Wakefield; Nerve Growth Factor Receptor p75 Expression in Basal Human Limbal and Pterygium Epithelium. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5301.
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The biological effects of neurotrophins (NTs) are mediated through cell-surface receptors known as the nerve growth factor receptors (NGFR) which include the low-affinity receptor p75 and high-affinity receptor TrkA. Previous studies in normal and diseased ocular tissue have localized TrkA in basal corneal, limbal, and conjunctival epithelium. While p75 expression was identified in subrabasal and full-thickness corneal epithelium. This study was initiated after identifying NGFR as one of several up-regulated genes in the human limbus by microarray analysis and we postulated that its expression may be indicative of a stem cell phenotype.
An immunohistochemical study was performed on diseased and normal human adult (n=15) and fetal (n=3) ocular surface epithelium using mono- and polyclonal antibodies to p75, TrkA, and nerve growth factor (NGF). Autologous limbal, conjunctival and pterygium tissue (n=10) was sectioned and immunohistochemically assessed. In vitro receptor expression was also established in three ocular surface epithelial cell types.
p75 was selectively expressed by basal epithelial cells in pterygia, conjunctiva, and limbus but was absent from the central cornea in all specimens. Notably, some staining was confined to the vascular endothelium. These results were confirmed with two other p75 antibodies. In contrast, TrkA immunoreactivity was found in full-thickness pterygium, conjunctival, and limbal epithelium in both adult and fetal ocular tissue. Mild epithelial reactivity for NGF was found in several (n=3) specimens. p75 expression was identified in less than 1%, while TrkA was found on the entire population of cultured conjunctival, limbal and pterygium-derived epithelial cells.
Contrary to previous studies, our results illustrate the selective p75 expression in basal pterygium, conjunctival, and limbal epithelium while staining was absent in adult and fetal corneas. We propose that p75 may represent an additional ocular-surface stem cell marker as others too have provided similar evidence in human oral and esophageal keratinocytes. Moreover, the expression of p75 in basal pterygium epithelium may reflect disregulated stem/progenitor cell activity in this disease.
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